Roflumilast Reduces Cerebral Inflammation in a Rat Model of Experimental Subarachnoid Hemorrhage

Inflammation. 2017 Aug;40(4):1245-1253. doi: 10.1007/s10753-017-0567-8.

Abstract

Roflumilast, a selective inhibitor for PDE4, is approved by FDA as an anti-inflammation drug for treatment of chronic obstructive pulmonary disease (COPD). This study investigates the effects of roflumilast on cerebral inflammation in the rat SAH model. Here, we show that subcutaneous administration of roflumilast (3 mg/kg) significantly improved the neurological deficits. Measurement of evans blue extravasation and brain water content revealed a significant reduction of blood-brain barrier permeability and brain edema. Importantly, roflumilast treatment remarkably decreased levels of IL-1β, IL-6, and TNF-α and the number of apoptotic neurons in the brain after SAH. These results indicate that roflumilast is effective in treating cerebral inflammation following SAH.

Keywords: cerebral inflammation; roflumilast; subarachnoid hemorrhage.

MeSH terms

  • Aminopyridines / pharmacology*
  • Aminopyridines / therapeutic use
  • Animals
  • Apoptosis / drug effects
  • Benzamides / pharmacology*
  • Benzamides / therapeutic use
  • Blood-Brain Barrier / drug effects
  • Brain / pathology*
  • Brain Edema / drug therapy
  • Cyclopropanes / pharmacology
  • Cyclopropanes / therapeutic use
  • Inflammation / prevention & control*
  • Inflammation Mediators
  • Permeability / drug effects
  • Phosphodiesterase 4 Inhibitors / pharmacology
  • Phosphodiesterase 4 Inhibitors / therapeutic use
  • Rats
  • Subarachnoid Hemorrhage / drug therapy
  • Subarachnoid Hemorrhage / pathology*

Substances

  • Aminopyridines
  • Benzamides
  • Cyclopropanes
  • Inflammation Mediators
  • Phosphodiesterase 4 Inhibitors
  • Roflumilast